tbuckley/cabot-search huggingface dataset:
An artificial intelligence based app for skin cancer detection evaluated in a population based setting
Authors: Anna M. Smak Gregoor, Tobias E. Sangers, Lytske J. Bakker, Loes Hollestein, Carin A. Uyl – de Groot, Tamar Nijsten, Marlies Wakkee
Journal: npj Digital Medicine (2023)

Artificial intelligence (AI) based algorithms for classification of suspicious skin lesions have been implemented in mobile phone apps (mHealth), but their effect on healthcare systems is undocumented. In 2019, a large Dutch health insurance company offered 2.2 million adults free access to an mHealth app for skin cancer detection. To study the impact on dermatological healthcare consumption, we conducted a retrospective population-based pragmatic study. We matched 18,960 mHealth-users who completed at least one successful assessment with the app to 56,880 controls who did not use the app and calculated odds ratios (OR) to compare dermatological claims between both groups in the first year after granting free access. A short-term cost-effectiveness analysis was performed to determine the cost per additional detected (pre)malignancy. Here we report that mHealth-users had more claims for (pre)malignant skin lesions than controls (6.0% vs 4.6%, OR 1.3 (95% CI 1.2-1.4)) and also a more than threefold higher risk of claims for benign skin tumors and nevi (5.9% vs 1.7%, OR 3.7 (95% CI 3.4-4.1)). The costs of detecting one additional (pre)malignant skin lesion with the app compared to the current standard of care were €2567. Based on these results, AI in mHealth appears to have a positive impact on detecting more cutaneous (pre)malignancies, but this should be balanced against the for now stronger increase in care consumption for benign skin tumors and nevi.
U.S. Law and Discrimination in Health Care
Authors: Kimani Paul-Emile
Journal: New England Journal of Medicine (2023)

Interview with Kimani Paul-Emile on U.S. laws aimed at protecting against discrimination in health care contexts and why such discrimination endures. (14:31)Download Although discrimination both by clinicians and by patients and families is relatively common in the United States, the laws that can be used to address these two types of discrimination differ substantially.
EZH2 mediated metabolic rewiring promotes tumor growth independently of histone methyltransferase activity in ovarian cancer
Authors: Jianfeng Chen, Jing Han Hong, Yulin Huang, Shini Liu, Jiaxin Yin, Peng Deng, Yichen Sun, Zhaoliang Yu, Xian Zeng, Rong Xiao, Jason Yongsheng Chan, Peiyong Guan, Yali Wang, Peili Wang, Lizhen Liu, Shijun Wen, Qiang Yu, Choon Kiat Ong, Bin-Tean Teh, Ying Xiong, Jing Tan
Journal: Molecular Cancer (2023)

Abstract Background Enhancer of zeste homolog 2 (EZH2), the key catalytic subunit of polycomb repressive complex 2 (PRC2), is overexpressed and plays an oncogenic role in various cancers through catalysis-dependent or catalysis-independent pathways. However, the related mechanisms contributing to ovarian cancer (OC) are not well understood. Methods The levels of EZH2 and H3K27me3 were evaluated in 105 OC patients by immunohistochemistry (IHC) staining, and these patients were stratified based on these levels. Canonical and noncanonical binding sites of EZH2 were defined by chromatin immunoprecipitation sequencing (ChIP-Seq). The EZH2 solo targets were obtained by integrative analysis of ChIP-Seq and RNA sequencing data. In vitro and in vivo experiments were performed to determine the role of EZH2 in OC growth. Results We showed that a subgroup of OC patients with high EZH2 expression but low H3K27me3 exhibited the worst prognosis, with limited therapeutic options. We demonstrated that induction of EZH2 degradation but not catalytic inhibition profoundly blocked OC cell proliferation and tumorigenicity in vitro and in vivo. Integrative analysis of genome-wide chromatin and transcriptome profiles revealed extensive EZH2 occupancy not only at genomic loci marked by H3K27me3 but also at promoters independent of PRC2, indicating a noncanonical role of EZH2 in OC. Mechanistically, EZH2 transcriptionally upregulated IDH2 to potentiate metabolic rewiring by enhancing tricarboxylic acid cycle (TCA cycle) activity, which contributed to the growth of OC. Conclusions These data reveal a novel oncogenic role of EZH2 in OC and identify potential therapeutic strategies for OC by targeting the noncatalytic activity of EZH2.
Hepatic glucuronyl C5-epimerase combats obesity by stabilising GDF15
Authors: Fei He, Haowen Jiang, Chang Peng, Tingting Wang, Rongrong Xiao, Meilin Chen, Nixue Song, Zhenyun Du, Hanlin Wang, Xiaoyu Ding, Yikai Shao, Jianping Fang, Yi Zang, Rong Hua, Jia Li, Kan Ding
Journal: Journal of Hepatology (2023)
The chemokine monocyte chemoattractant protein-1/CCL2 is a promoter of breast cancer metastasis
Authors: Teizo Yoshimura, Chunning Li, Yuze Wang, Akihiro Matsukawa
Journal: Cellular and Molecular Immunology (2023)

Abstract Breast cancer is the most prevalent cancer worldwide, and metastasis is the leading cause of death in cancer patients. Human monocyte chemoattractant protein-1 (MCP-1/CCL2) was isolated from the culture supernatants of not only mitogen-activated peripheral blood mononuclear leukocytes but also malignant glioma cells based on its in vitro chemotactic activity toward human monocytes. MCP-1 was subsequently found to be identical to a previously described tumor cell-derived chemotactic factor thought to be responsible for the accumulation of tumor-associated macrophages (TAMs), and it became a candidate target of clinical intervention; however, the role of TAMs in cancer development was still controversial at the time of the discovery of MCP-1. The in vivo role of MCP-1 in cancer progression was first evaluated by examining human cancer tissues, including breast cancers. Positive correlations between the level of MCP-1 production in tumors and the degree of TAM infiltration and cancer progression were established. The contribution of MCP-1 to the growth of primary tumors and metastasis to the lung, bone, and brain was examined in mouse breast cancer models. The results of these studies strongly suggested that MCP-1 is a promoter of breast cancer metastasis to the lung and brain but not bone. Potential mechanisms of MCP-1 production in the breast cancer microenvironment have also been reported. In the present manuscript, we review studies in which the role of MCP-1 in breast cancer development and progression and the mechanisms of its production were examined and attempt to draw a consensus and discuss the potential use of MCP-1 as a biomarker for diagnosis.
Ontologizing health systems data at scale: making translational discovery a reality
Authors: Tiffany J. Callahan, Adrianne L. Stefanski, Jordan M. Wyrwa, Chenjie Zeng, Anna Ostropolets, Juan M. Banda, William A. Baumgartner, Richard D. Boyce, Elena Casiraghi, Ben D. Coleman, Janine H. Collins, Sara J. Deakyne Davies, James A. Feinstein, Asiyah Y. Lin, Blake Martin, Nicolas A. Matentzoglu, Daniella Meeker, Justin Reese, Jessica Sinclair, Sanya B. Taneja, Katy E. Trinkley, Nicole A. Vasilevsky, Andrew E. Williams, Xingmin A. Zhang, Joshua C. Denny, Patrick B. Ryan, George Hripcsak, Tellen D. Bennett, Melissa A. Haendel, Peter N. Robinson, Lawrence E. Hunter, Michael G. Kahn
Journal: npj Digital Medicine (2023)

Abstract Common data models solve many challenges of standardizing electronic health record (EHR) data but are unable to semantically integrate all of the resources needed for deep phenotyping. Open Biological and Biomedical Ontology (OBO) Foundry ontologies provide computable representations of biological knowledge and enable the integration of heterogeneous data. However, mapping EHR data to OBO ontologies requires significant manual curation and domain expertise. We introduce OMOP2OBO, an algorithm for mapping Observational Medical Outcomes Partnership (OMOP) vocabularies to OBO ontologies. Using OMOP2OBO, we produced mappings for 92,367 conditions, 8611 drug ingredients, and 10,673 measurement results, which covered 68–99% of concepts used in clinical practice when examined across 24 hospitals. When used to phenotype rare disease patients, the mappings helped systematically identify undiagnosed patients who might benefit from genetic testing. By aligning OMOP vocabularies to OBO ontologies our algorithm presents new opportunities to advance EHR-based deep phenotyping.
Virulence factor genes and antimicrobial susceptibility of Staphylococcus lugdunensis strains
Authors: Anna Budzyńska, Natalia Wiktorczyk-Kapischke, Katarzyna Grudlewska-Buda, Patrycja Erdmańska, Katarzyna Boczkowska, Ewa Wałecka-Zacharska, Eugenia Gospodarek-Komkowska, Krzysztof Skowron
Journal: Journal of Infection (2023)
Morphine Re-Arranges Chromatin Spatial Architecture of Primate Cortical Neurons
Authors: Liang Wang, Xiaojie Wang, Chunqi Liu, Wei Xu, Weihong Kuang, Qian Bu, Hongchun Li, Ying Zhao, Linhong Jiang, Yaxing Chen, Feng Qin, Shu Li, Qinfan Wei, Xiaocong Liu, Bin Liu, Yuanyuan Chen, Yanping Dai, Hongbo Wang, Jingwei Tian, Gang Cao, Yinglan Zhao, Xiaobo Cen
Journal: Genomics Proteomics & Bioinformatics (2023)

The expression of linear DNA sequence is precisely regulated by the three-dimensional (3D) architecture of chromatin. Morphine-induced aberrant gene networks of neurons have been extensively investigated; however, how morphine impacts the 3D genomic architecture of neurons is still unknown. Here, we applied digestion-ligation-only high-throughput chromosome conformation capture (DLO Hi-C) technology to investigate the effects of morphine on the 3D chromatin architecture of primate cortical neurons. After receiving continuous morphine administration for 90 days on rhesus monkeys, we discovered that morphine re-arranged chromosome territories, with a total of 391 segmented compartments being switched. Morphine altered over half of the detected topologically associated domains (TADs), most of which exhibited a variety of shifts, followed by separating and fusing types. Analysis of the looping events at kilobase-scale resolution revealed that morphine increased not only the number but also the length of differential loops. Moreover, all identified differentially expressed genes from the RNA sequencing data were mapped to the specific TAD boundaries or differential loops, and were further validated for changed expression. Collectively, an altered 3D genomic architecture of cortical neurons may regulate the gene networks associated with morphine effects. Our finding provides critical hubs connecting chromosome spatial organization and gene networks associated with the morphine effects in humans.
Self‐Assembly Induced Photosensitization of Long‐Tailed Heavy‐Atom‐Free BODIPY Derivatives for Photodynamic Therapy
Authors: Jigai li, Xianfa Du, Xin Zhou, Juyoung Yoon
Journal: Advanced Healthcare Materials (2023)

Abstract Type I photosensitizers (PSs) are a promising approach for photodynamic therapy (PDT) since they can generate radicals that are tolerant to hypoxia. Thus, the development of highly efficient type I PSs is essential. Self‐assembly is a promising strategy for developing novel PSs with desirable properties. Here, a simple and effective approach is developed to create heavy‐atom‐free PSs for PDT by self‐assembling long‐tailed boron dipyrromethene dyes (BODIPYs). The resulting aggregates BY‐I16 and BY‐I18 can efficiently convert their excited energy to the triplet state, producing reactive oxygen species that are essential for PDT. Furthermore, the aggregation and PDT performance can be regulated by adjusting the length of the tailed alkyl chains. As proof of concept, the efficacy of these heavy‐atom‐free PSs both in vitro and in vivo under both normoxic and hypoxic conditions is demonstrated.
A Dual-Chamber Leadless Pacemaker
Authors: Reinoud E. Knops, Vivek Y. Reddy, James E. Ip, Rahul Doshi, Derek V. Exner, Pascal Defaye, Robert Canby, Maria Grazia Bongiorni, Morio Shoda, Gerhard Hindricks, Petr Neužil, Mayer Rashtian, Karel T.N. Breeman, Jordan R. Nevo, Leonard Ganz, Chris Hubbard, Daniel J. Cantillon
Journal: New England Journal of Medicine (2023)

Single-chamber ventricular leadless pacemakers do not support atrial pacing or consistent atrioventricular synchrony. A dual-chamber leadless pacemaker system consisting of two devices implanted percutaneously, one in the right atrium and one in the right ventricle, would make leadless pacemaker therapy a treatment option for a wider range of indications.
Cholesterol Metabolism Modulation Nanoplatform Improves Photo‐Immunotherapeutic Effect in Oral Squamous Cell Carcinoma
Authors: Xinyu Zhang, Zichen Cao, Chuanhui Song, Zheng Wei, Meng Zhou, Si Chen, Jianchuan Ran, Hongbo Zhang, Huihui Zou, Shengwei Han, Yu Cai, Wei Han
Journal: Advanced Healthcare Materials (2023)

Impressive results in cancer treatment have been obtained through immunotherapy. However, abnormally high cholesterol metabolism in the tumor microenvironment (TME) leads to poor immunogenicity or even immunosuppression, which dramatically reduces the clinical response of patients with oral squamous cell carcinoma (OSCC) to immunotherapy. In this study, a cholesterol-modulating nanoplatform (PYT NP) is developed to restore the normal immune microenvironment, significantly inhibiting SQLE (an essential gene for cholesterol biosynthesis in tumor cells) by releasing terbinafine, thereby reducing cholesterol in the TME and suppressing tumor cell proliferation. In addition, the nanoplatform is equipped with a second near-infrared (NIR-II) photosensitizer, Y8, which triggers immunogenic cell death of tumor cells, thereby promoting intra-tumor infiltration and immune activation via the production of damage-associated molecular patterns for photoimmunotherapy. PYT NPs show great promise in stimulating strong cholesterol-modulating anticancer immunity combined with photoimmunotherapy, opening up a new avenue for sensitized OSCC immunotherapy.
The multifunctional human ocular melanocortin system
Authors: Chieh-Lin (Stanley) Wu, Adrian V. Cioanca, Maria C. Gelmi, Li Wen, Nick Di Girolamo, Ling Zhu, Riccardo Natoli, R Max Conway, Constantinos Petsoglou, Martine J. Jager, Peter J. McCluskey, Michele C. Madigan
Journal: Progress in Retinal and Eye Research (2023)
Brief Report: Severe Sotorasib-Related Hepatotoxicity and Non-Liver Adverse Events Associated With Sequential Anti–Programmed Cell Death (Ligand)1 and Sotorasib Therapy in KRASG12C-Mutant Lung Cancer
Authors: Ali Chour, Julie Denis, Céline Mascaux, Maeva Zysman, Laurence Bigay-Game, Aurélie Swalduz, Valérie Gounant, Alexis Cortot, Marie Darrason, Vincent Fallet, Edouard Auclin, Clémence Basse, Claire Tissot, Chantal Decroisette, Pierre Bombaron, Etienne Giroux-Leprieur, Luc Odier, Solenn Brosseau, Quentin Creusot, Marina Gueçamburu, Corentin Meersseman, Adrien Rochand, Adrien Costantini, Claire Marine Gaillard, Eric Wasielewski, Nicolas Girard, Jacques Cadranel, Claire Lafitte, Fanny Lebossé, Michaël Duruisseaux
Journal: Journal of Thoracic Oncology (2023)
First-in-Human Experience With Impella 5.0/5.5 for High-Risk Patients With Advanced Heart Failure Undergoing VT Ablation
Authors: Jakub Sroubek, Ramya Vajapey, Joseph J. Sipko, Edward G. Soltesz, Aaron J. Weiss, Mandeep Bhargava, Ayman A. Hussein, Mohamed Kanj, Walid I. Saliba, Tyler L. Taigen, Oussama M. Wazni, Pasquale Santangeli
Journal: Journal of the American College of Cardiology (2023)
A population pharmacokinetic model of polymyxin B based on prospective clinical data to inform dosing in hospitalized patients
Authors: Patrick O. Hanafin, Andrea Kwa, Alexandre P. Zavascki, Ana Maria Sandri, Marc H. Scheetz, Christine J. Kubin, Jayesh Shah, Benjamin P.Z. Cherng, Michael T. Yin, Jiping Wang, Lu Wang, David P. Calfee, Maureen Bolon, Jason M. Pogue, Anthony W. Purcell, Roger L. Nation, Jian Li, Keith S. Kaye, Gauri G. Rao
Journal: Clinical Microbiology and Infection (2023)
Remote haemodynamic monitoring of pulmonary artery pressures in patients with chronic heart failure (MONITOR-HF): a randomised clinical trial
Authors: Jasper J Brugts, Sumant P Radhoe, Pascal R D Clephas, Dilan Aydin, Marco W F van Gent, Mariusz K Szymanski, Michiel Rienstra, Mieke H van den Heuvel, Carlos A da Fonseca, Gerard C M Linssen, C Jan Willem Borleffs, Eric Boersma, Folkert W Asselbergs, Arend Mosterd, Hans-Peter Brunner-La Rocca, Rudolf A de Boer, M E Emans, S L M A Beeres, L Heerebeek, C Kirchhof, J Van Ramshorst, R Spee, T Smilde, M Van Eck, E Kaplan, R Hazeleger, R Tukkie, M Feenema, W Kok, V Van Halm, M L Handoko, R Van Kimmenade, M Post, N Van Mieghem, O C Manintveld
Journal: The Lancet (2023)
lncRNA SYTL5-OT4 promotes vessel co-option by inhibiting the autophagic degradation of ASCT2
Authors: Qing Wen, Maohua Huang, Jingwen Xie, Runyu Liu, Qun Miao, Jinjun Huang, Junqiu Zhang, Wenyu lyu, Ming Qi, Chunyi Wu, Qi Qi, Zhijing Zhang, Rong Deng, Chenran Wang, Zhe-Sheng Chen, Dongmei Zhang, Wencai Ye, Minfeng Chen
Journal: Drug Resistance Updates (2023)

Vessel co-option is responsible for tumor resistance to antiangiogenic therapies (AATs) in patients with colorectal cancer liver metastasis (CRCLM). However, the mechanisms underlying vessel co-option remain largely unknown. Herein, we investigated the roles of a novel lncRNA SYTL5-OT4 and Alanine-Serine-Cysteine Transporter 2 (ASCT2) in vessel co-option-mediated AAT resistance.SYTL5-OT4 was identified by RNA-sequencing and verified by RT-qPCR and RNA fluorescence in situ hybridization assays. The effects of SYTL5-OT4 and ASCT2 on tumor cells were investigated by gain- and loss-of-function experiments, and those of SYTL5-OT4 on ASCT2 expression were analyzed by RNA immunoprecipitation and co-immunoprecipitation assays. The roles of SYTL5-OT4 and ASCT2 in vessel co-option were detected by histological, immunohistochemical, and immunofluorescence analyses.The expression of SYTL5-OT4 and ASCT2 was higher in patients with AAT-resistant CRCLM. SYTL5-OT4 enhanced the expression of ASCT2 by inhibiting its autophagic degradation. SYTL5-OT4 and ASCT2 promoted vessel co-option by increasing the proliferation and epithelial-mesenchymal transition of tumor cells. Combination therapy of ASCT2 inhibitor and antiangiogenic agents overcame vessel co-option-mediated AAT resistance in CRCLM.This study highlights the crucial roles of lncRNA and glutamine metabolism in vessel co-option and provides a potential therapeutic strategy for patients with AAT-resistant CRCLM.
Osteoimmunomodulatory GelMA/liposome coatings to promote bone regeneration of orthopedic implants
Authors: F. Jahanmard, A. Khodaei, J. Flapper, O. Dogan, K. Roohi, P. Taheri, H. Weinans, G. Storm, M. Croes, E. Mastrobattista, S. Amin Yavari
Journal: Journal of Controlled Release (2023)

Despite being the most widely used biomaterials in orthopedic surgery, metallic implants do not induce new bone growth because they are bioinert. Surface biofunctionalization of implants with immunomodulatory mediators is a recent approach to promote osteogenic factors that facilitate bone regeneration. Liposomes (Lip) can be used as a low-cost, efficient and simple immunomodulator to stimulate immune cells in favor of bone regeneration. Even though liposomal coating systems have been reported previously, their main disadvantage is their limited ability to preserve liposome integrity after drying. In order to address this issue, we developed a hybrid system in which liposomes could be embedded in a polymeric hydrogel namely gelatin methacryloyl (GelMA). Specifically, we have developed a novel versatile coating strategy using electrospray technology to coat implants with GelMA/Liposome without using adhesive intermediate layer. The two differently charged Lip (i.e., anionic and cationic) were blended with GelMA and coated via electrospray technology on the bone-implant surfaces. The results showed that the developed coating withstood mechanical stress during surgical replacement, and Lip inside GelMA coating stayed intact in different storage conditions for a minimum of 4 weeks. Surprisingly, bare Lip, either cationic or anionic, improved the osteogenesis of human Mesenchymal Stem Cells (MSCs) by inducing pro-inflammatory cytokines, even at a low dosage of Lip released from the GelMA coating. More importantly, we showed that the inflammatory response could be fine-tuned by selecting the Lip concentration, Lip/hydrogel ratio, and coating thickness to determine the timing of the release such that we can accommodate different clinical needs. These promising results pave the way to use these Lip coatings to load different types of therapeutic cargo for bone-implant applications.
Ammonium trifluoroborate-modified poly(β-aminoesters): A case study for PET-guided in vivo pharmacokinetic studies of a non-viral gene delivery system
Authors: Raúl Cosialls, Odile Fernández, Cristina Simó, Krishna R. Pulagam, Marta Guerra-Rebollo, Jordi Llop, Cristina Fornaguera, Ana B. Cuenca, Salvador Borrós
Journal: Journal of Controlled Release (2023)
Effects of dapagliflozin on heart failure hospitalizations according to severity of inpatient course: Insights from <scp>DELIVER</scp> and <scp>DAPA‐HF</scp>
Authors: Safia Chatur, Toru Kondo, Brian L. Claggett, Kieran Docherty, Zi Michael Miao, Akshay S. Desai, Pardeep S. Jhund, Rudolf A. de Boer, Adrian F. Hernandez, Silvio E. Inzucchi, Mikhail N. Kosiborod, Carolyn S.P. Lam, Felipe A. Martinez, Sanjiv J. Shah, Magnus Petersson, Anna Maria Langkilde, John J.V. McMurray, Scott D. Solomon, Muthiah Vaduganathan
Journal: European Journal of Heart Failure (2023)

Dapagliflozin resulted in significant and sustained reductions in first and recurrent heart failure (HF) hospitalizations among patients with HF across the spectrum of ejection fraction. How treatment with dapagliflozin differentially impacts hospitalization for HF of varying complexity is not well studied.In the DELIVER and DAPA-HF trials, we examined the effects of dapagliflozin on adjudicated HF hospitalizations of varying complexity and hospital length of stay (LOS). HF hospitalizations requiring intensive care unit stay, intravenous vasoactive therapies, invasive/non-invasive ventilation, mechanical fluid removal or mechanical circulatory support were categorized as complicated. The balance was classified as uncomplicated. Of the total 1209 HF hospitalizations reported in DELIVER, 854 (71%) were uncomplicated and 355 (29%) were complicated. Of the total 799 HF hospitalizations reported in DAPA-HF, 453 (57%) were uncomplicated and 346 (43%) were complicated. Relative to patients experiencing a first uncomplicated HF hospitalization, those with complicated HF hospitalizations had a significantly higher in-hospital mortality both in DELIVER (16.7% vs. 2.3%, p < 0.001) and DAPA-HF (15.1% vs. 3.8%, p < 0.001). Dapagliflozin similarly reduced total 'uncomplicated' (DELIVER: rate ratio [RR] 0.67, 95% confidence interval [CI] 0.55-0.82 and DAPA-HF: RR 0.69, 95% CI 0.54-0.87) and 'complicated' HF hospitalizations (DELIVER: RR 0.82, 95% CI 0.63-1.06 and DAPA-HF: RR 0.75, 95% CI 0.58-0.97). Dapagliflozin consistently reduced hospitalizations irrespective of their LOS: <5 days (DELIVER: RR 0.76, 95% CI 0.58-0.99 and DAPA-HF: RR 0.58, 95% CI 0.42-0.80) or ≥5 days (DELIVER: RR 0.71, 95% CI 0.58-0.86 and DAPA-HF: RR 0.77, 95% CI 0.62-0.94).A substantial proportion of hospitalizations (∼30-40%) among patients with HF irrespective of ejection fraction required intensification of treatment beyond standard intravenous diuretics. Such patients experienced significantly higher in-hospital mortality. Treatment with dapagliflozin consistently reduced HF hospitalizations regardless of severity of inpatient course or LOS.ClinicalTrials.gov, DELIVER (NCT03619213) and DAPA-HF (NCT03036124).